Synergistic regulation of fetal rat liver nicotinamide adenine dinucleotide phosphate (reduced form) cytochrome c reductase activity: effects of L-triiodothyronine and hydrocortisone.
The activity of hepatic NADPH cytochrome c reductase, an enzyme important in drug and steroid metabolism, increases rapidly during the perinatal period in rats. However, the regulation of this increase is not well understood. To investigate the role of hormones in the development of NADPH cytochrome c reductase activity, fetal rat livers in organ culture were used in the present study. Explants from 20-day-old fetal rat liver could be maintained for up to 96 h in a serum-free medium with or without added hormones. When the explants were exposed to 50 nM L-T3 for 72 h, they had 74% greater NADPH cytochrome c reductase activity than controls. In contrast, 1 microM hydrocortisone (HC) stimulated reductase activity by only 20%. However, when T3 was added with HC there was a synergistic effect, resulting in a 167% elevation in NADPh cytochrome c reductase activity. The response to T3 plus HC was detectable after 24 h and maximal after 72 h. Control activity rose slightly during the first 48 h in culture and was stable thereafter. Stimulation of reductase activity by T3 was detectable at 0.1 nM, half maximal at 2 nM, and maximal between 10 nM and 100 nM. T4 also stimulated NADPh cytochrome c reductase activity in explants but was only 3-4% as potent as T3. The effect of steroids was specific for glucocorticoids. Neither glucagon nor insulin had any measurable effect on reductase activity. Electron micrographs revealed that hepatic ultrastructure was well preserved for at least 72 h of incubation in the presence or absence of hormones. The data suggest, therefore, that the normal perinatal development of hepatic NADPH cytochrome c reductase activity in rats is regulated at least in part by thyroid hormones acting synergistically with glucocorticoids.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000201:enzymology*; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000196:embryology; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000494:pharmacology; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D009251:NADPH-Ferrihemoprotein Reductase; D013974:Thyroxine; D006854:Hydrocortisone